TRDMT1 exhibited protective effects against LPS ‐induced inflammation in rats through TLR4‐NF‐κB / MAPK‐TNF ‐α pathway

作者：Zhengguang Li, Xiaolong Qi, Xu Zhang, Lei Yu, Lijuan Gao, Weining Kong, Wei Chen, Wei Dong, Lijun Luo, Dan Lü, Lianfeng Zhang, Yuanwu Ma · 发表于：Animal Models and Experimental Medicine · 年份：2022 · DOI：10.1002/ame2.12221 · 被引用次数：29 · 研究领域：RNA modifications and cancer、Cancer-related gene regulation、Epigenetics and DNA Methylation

BACKGROUND: Inflammation is a complex physiological and pathological process. Although many types of inflammation are well characterized, their physiological functions are largely unknown. tRNA aspartic acid methyltransferase 1 (TRDMT1) has been implicated as a stress-related protein, but its intrinsic biological role is unclear. METHODS: We constructed a Trdmt1 knockout rat and adopted the LPS-induced sepsis model. Survival curve, histopathological examination, expression of inflammatory factors, and protein level of TLR4 pathway were analyzed. RESULTS: Trdmt1 deletion had no obvious impact on development and growth. Trdmt1 deletion slightly increased the mortality during aging. Our data showed that Trdmt1 strongly responded in LPS-treated rats, and Trdmt1 knockout rats were vulnerable to LPS treatment with declined survival rate. We also observed more aggravated tissue damage and more cumulative functional cell degeneration in LPS-treated knockout rats compared with control rats. Further studies showed upregulated TNF-α level in liver, spleen, lung, and serum tissues, which may be explained by enhanced p65 and p38 phosphorylation. CONCLUSIONS: Our data demonstrated that Trdmt1 plays a protective role in inflammation by regulating the TLR4-NF-κB/MAPK-TNF-α pathway. This work provides useful information to understand the TRDMT1 function in inflammation.